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Antiinflammatory and anticoagulant effects of transgenic expression of human thrombomodulin in mice

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Version 2 2024-06-03, 18:14
Version 1 2019-03-08, 10:47
journal contribution
posted on 2024-06-03, 18:14 authored by S Crikis, XM Zhang, S Dezfouli, KM Dwyer, LM Murray-Segal, E Salvaris, C Selan, SC Robson, HH Nandurkar, PJ Cowan, AJF d'Apice
Thrombomodulin (TBM) is an important vascular anticoagulant that has species specific effects. When expressed as a transgene in pigs, human (h)TBM might abrogate thrombotic manifestations of acute vascular rejection (AVR) that occur when GalT-KO and/or complement regulator transgenic pig organs are transplanted to primates. hTBM transgenic mice were generated and characterized to determine whether this approach might show benefit without the development of deleterious hemorrhagic phenotypes. hTBM mice are viable and are not subject to spontaneous hemorrhage, although they have a prolonged bleeding time. They are resistant to intravenous collagen-induced pulmonary thromboembolism, stasis-induced venous thrombosis and pulmonary embolism. Cardiac grafts from hTBM mice to rats treated with cyclosporine in a model of AVR have prolonged survival compared to controls. hTBM reduced the inflammatory reaction in the vein wall in the stasis-induced thrombosis and mouse-to-rat xenograft models and reduced HMGB1 levels in LPS-treated mice. These results indicate that transgenic expression of hTBM has anticoagulant and antiinflammatory effects that are graft-protective in murine models.

History

Journal

American journal of transplantation

Volume

10

Pagination

242-250

Location

Chichester, Eng.

Open access

  • Yes

eISSN

1600-6143

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2010, The Authors

Issue

2

Publisher

John Wiley & Sons